# Prenatal and Postnatal Exposure to Environmental Mixtures: Neurodevelopment and DNA Methylation Biomarkers

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $136,842

## Abstract

PROJECT SUMMARY
Prenatal and postnatal childhood exposure to metals, essential and non-essential, is ubiquitous via dietary and
environmental sources. Heavy metals, including lead and methylmercury, are well characterized as potent
neurotoxicants, associated with lower cognition and poor learning abilities. Yet, our understanding of the
neurotoxicity and joint impact of many other common prenatal and postnatal metal exposures remains extremely
limited. Even less is known about the combined impact of exposure to multiple metals during fetal development
or postnatal exposure during early childhood, or the influence of other environmental mixtures such as nutrients,
which may have shared sources, on the neurodevelopmental effects of metals. To address this significant gap,
our long-term goal is to quantify the neurocognitive impact of ubiquitous prenatal and postnatal environmental
mixtures and identify cord blood DNA methylation biomarkers that can reconstruct prenatal environmental
exposures and predict future neurocognitive development in children. We will test if objective measures of key
prenatal maternal nutrients, such as folate, vitamin B12 and essential metals attenuate or mitigate the
neurotoxicity of metal mixtures. To accomplish this goal, we will leverage resources from an established U.S.
pre-birth cohort, Project Viva. In this cohort, we have measured concentrations for 14 prenatal maternal metals
in the first trimester of pregnancy and blood samples collected in early-childhood (~3 years) ready for metal
testing as well as ready to use genome-wide cord blood DNA methylation screens. Children have been followed
prospectively and undergone detail testing for neurodevelopment in early (~3 years of age) and mid-childhood
(~7 years). We hypothesize that prenatal maternal 1st trimester and postnatal early childhood neurotoxic metal
mixtures are associated with poor neurodevelopment in early and mid-childhood (Aim 1), and that prenatal first
trimester maternal plasma folate, vitamin B12 and blood concentration of essential metals protect against
prenatal metal mixture neurotoxicity (Aim 2). We also hypothesize that DNA methylation marks measured in
umbilical cord blood at birth can reconstruct prenatal exposure to metals (Aim 3.a) and that cord blood DNAm
marks predict future neurocognitive development in early and mid-childhood (Aim 3.b). By testing longitudinal
associations in a large cohort of children with detail cognitive assessments as well as objective biomarkers of
metals and nutrients, we will overcome limitations currently faced by existing studies testing few exposures
simultaneously. We will use novel statistical methodology to model prenatal and postnatal environmental
mixtures and machine learning algorithms to build epigenetic predictors of exposure and neurodevelopment.
This research will provide a comprehensive quantification of the cognitive burden of prenatal and postnatal
mixtures, the development of biomarkers of exposu...

## Key facts

- **NIH application ID:** 10376348
- **Project number:** 5R01ES031259-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Andres Cardenas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $136,842
- **Award type:** 5
- **Project period:** 2020-06-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376348

## Citation

> US National Institutes of Health, RePORTER application 10376348, Prenatal and Postnatal Exposure to Environmental Mixtures: Neurodevelopment and DNA Methylation Biomarkers (5R01ES031259-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376348. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*